This research investigates the genetic basis of male sexual motivation and behavior. Behaviors leading to sexual reproduction are essential for the survival of most animal species, yet little is presently known about how the nervous system generates appropriate motivational states and appetitive and consummatory sexual behaviors. One approach to understanding animal behavior is to identify essential genes and study their cellular expression patterns and molecular functions. In order to identify genes required for male sexual behavior, mutants defective in both appetitive and consummatory phases of sexual behavior will be identified in the soil round worm Caenorhabditis elegans, a well-defined invertebrate genetic model organism. Preliminary studies have established a quantitative behavioral assay for a putative mate-searching behavior of the adult C. elegans male. The assay has been used to show that expression of mate-searching behavior is regulated by presence or absence of suitable mates, nutritional status, and signals from the reproductive system. The results are interpreted to indicate that mate-searching is potentiated by a regulated state of the nervous system that we define as the nematode analog of a sex drive motivational state of higher animals. Genetic screens will be performed to identify new mutants of two types: mutants in which males fail to express mate-searching behavior and mutants in which males exhibit sex drive yet fail to copulate. Selective genes identified will be molecularly cloned and the identity and expression patterns of their products defined. Among three mate-searching-defective genetic loci already identified, one encodes the C. elegans homolog of the serotonin reuptake transporter, the target in both humans and nematodes of fluoxetine antidepressants. In view of the sexual dysfunction caused by fluoxetine administration in humans, this result suggests that these studies may have relevance to understanding motivated sexual behavior in humans and thus may have potential clinical implications.